Chronic inflammatory, autoimmune, and cancer diseases are major health problems in the Western world and becoming increasingly so in developing countries. These diseases include rheumatic conditions, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The latter is often described as a prototypic systemic autoimmune disease, and more than 80 autoimmune rheumatic diseases have been described, cf. e.g. Harrison's Principles of Internal Medicine, 17th Edition.
Rheumatoid arthritis is a chronic inflammatory disease that affects 0.5-1% of the general population1. Cardiovascular disease (CVD) represents a major source of serious morbidity and mortality and accounts for an increase in risk of approximately 60% for all RA-related deaths2. Recently it was suggested that RA may be equal to diabetes mellitus type 2 as an independent risk factor for CVD3. Traditional Framingham risk factors and inflammation-associated factors may contribute to increased risk of CVD in RA4.
Cancer diseases represent a substantial challenge to the health care system and communities due to the high costs associated with treatment. The majority of patients experience a decrease of life quality during treatment. Some of the cancer diseases may be treated by biologic agents, which may be associated with side effects.
In recent years, the treatment of RA has improved due to the introduction of biologics, including tumor necrosis factor (TNF) antagonists and B-cell-targeting agents such as rituximab. Several studies consistently indicate that anti-TNF treatment ameliorates the risk of CVD5. The effect of TNF blockade on the cardiovascular functions, such as, for example, arterial stiffness, is not clear, and there are both positive6 and negative studies7. In addition, suppression of inflammation in RA by TNF blockade has been shown to induce pro-atherogenic changes in lipid profiles8, but data on short-term and long-term effects remain inconsistent9.
Rituximab inhibits B-cell function by targeting CD20, and is increasingly used in rheumatic and autoimmune diseases, including RA, especially for treatment of patients who do not respond to anti-TNF treatment10. Little is known about the exact role of B cells in CVD and atherosclerosis, but both pro- and anti-atherogenic effects have been suggested11-13. Recent studies indicate that short-term treatment with rituximab improves vascular function and dyslipidemia14; moreover, it decreases pro-thrombotic biomarkers15. Thus, anti-CD20 treatment may reduce future CVD risks in RA, but data are limited.
It has recently been reported that low levels of IgM natural antibodies against phosphorylcholine (anti-PC) independently predict CVD16-18 and that there is a negative association between anti-PC levels and development of human atherosclerosis19. Further, low levels of IgM anti-PC were associated with systemic lupus erythematosus (SLE) in a nested case-control SLE-study20. No studies addressing anti-PC in RA and effects of anti-TNF treatment have been performed. Anti-CD20 treatment has been shown to decrease total immunoglobulin, mostly IgM, and to induce heterogeneous effects on antibody levels in rheumatic diseases21. The effects of B-cell depletion on anti-PC levels are still not known.
It is here reported how treatment with biologic agents, such as etanercept, infliximab, adalimumab and rituximab, during one year influences levels of IgM anti-PC, oxidized low-density lipoprotein (oxLDL) and the apolipoprotein profile.